Single molecule tracking analysis reveals that the surface mobility of amyloid oligomers is driven by their conformational structure.

Several models have been proposed to explain the cytotoxicity of Aβ oligomers. The structural polymorphism of the oligomers can account for the various toxic effects observed. By combining the use of conformation-specific antibodies and single particle tracking techniques, we have investigated the mobility of individual Aβ1-42 oligomers on the plasma membrane of living cells. Distinct structural types of Aβ1-42 oligomers were labeled with two different conformation-specific antibodies. While both types of oligomers showed a heterogeneous dynamic behavior, their overall mobility was found to be significantly different. Conversely, we discovered that other amyloid oligomers sharing a similar conformation but composed of different peptides (amylin and prion Sup35NM) display dynamic behaviors comparable to those found for Aβ1-42 oligomers. This study provides evidence for a link between the quaternary structure and the membrane mobility of proteins, revealing that structurally analogous supramolecular assemblies diffuse similarly in cells.